A tetradecapeptide somatostatin dicarba-analog: Synthesis, structural impact and biological activity.

PABLO MARTÍN-GAGO; ROSARIO RAMÓN; ERIC ARAGON; JIMENA FERNANDEZ-CARNEADO; XAVIER VERDAGUER; PILAR LÓPEZ-RUIZ; BEGOÑA COLÁS; MARÍA A. CORTÉS; BERTA PONSATI; MARIA J. MACIAS; ANTONI RIERA

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014 vol. 24 p. 103 - 107

0960-894X

Factor de impacto 2013: 2.331 Ranking Q2 We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization between allylGly 3 and 14 proceeded in moderate yield, excellent cyclic/linear ratio and very high Z-double bond selectivity. NMR studies also demonstrated that the conformational flexibility of this peptide is increased in comparison to that of the natural hormone. Remarkably, this alkene-bridged somatostatin analog is highly selective against somatostatin receptors 1 and 5, suggesting that conformational rigidity is not required for the efficient interaction of somatostatin analogues with these two receptors.